We have demonstrated that the human placenta synthesizes a molecule very similar or identical to luteinizing hormone releasing hormone (LRH). This placental LRH (pLRH) has physiochemical, immunological and biological activities indistinguishable from synthetic LRH (pLRH). On the basis of preliminary studies during pregnancy, both in vivo and in vitro, we have hypothesized that pLRH regulates the release of chorionic gonadotropin (CG) and steroid production during pregnancy. In this project we are proposing to determine the precise chemical nature of pLRH, i.e. its amino acid composition and primary structure and to compare it to sLRH. We will also determine the biologic potency of pLRH to release LH and FSH in the non-pregnant rat, as compared to sLRH. In addition, the biologic activity of LRH during pregnancy will be studied, both in vivo and in vitro. Using human placental explant cultures the dose response of human CG, human chorionic somatomammotropin (hCS), progesterone, estrone, estradiol and estriol to sLRH will be determined for placentas of varying gestational states. Similar studies will be done using pLRH and its potency compared to that for sLRH. In vivo studies on the effect of sLRH on circulating levels of CGs and steroids will be investigated in pregnant monkeys and humans at different gestational ages. The dose-response of these hormonal parameters to sLRH will be determined for each gestational age and differences at the various stages of pregnancy analyzed. In the pregnant monkey the potency of pLRH in affecting these hormonal parameters will be compared to sLRH. These data will provide basic information concerning the chemical nature of pLRH and the biologic activity of LRH during pregnancy. This information will form the basis of proposing the function(s) of LRH in pregnancy and its possible use(s) for the maintenance or termination of pregnancy.